Identification of age-related Human Blood factors as a therapeutic target for Alzheimer's disease

Projektinformationen

HeBe

ID Finanzhilfevereinbarung: 948677

DOI

10.3030/948677

Projekt abgeschlossen

EK-Unterschriftsdatum 10 November 2020

Startdatum 1 April 2021

Enddatum 31 März 2026

Finanziert unter

• EXCELLENT SCIENCE - European Research Council (ERC)

Gesamtkosten

€ 1 498 915,00

EU-Beitrag

€ 1 498 915,00

Koordiniert durch

FUNDACIO BARCELONABETA BRAIN RESEARCH CENTER
Spain

Periodic Reporting for period 3 - HeBe (Identification of age-related Human Blood factors as a therapeutic target for Alzheimer's disease)

Berichtszeitraum: 2024-04-01 bis 2025-09-30

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

The HeBe project seeks to uncover potential therapeutic targets for Alzheimer's disease by investigating blood factors influencing brain ageing. Inspired by findings in mice, where some blood factors rejuvenated aging brains, the project takes a novel approach. We will investigate the blood from individuals that have a younger brain age and an older brain age than expected. By utilizing advanced proteomics and metabolomics, HeBe aims to identify blood factors associated with brain ageing and neurodegeneration. The project's central hypothesis posits that certain blood factors may influence the rate of neurodegeneration. If confirmed, this insight could pave the way for novel therapeutic avenues. The ultimate goal is to design a proof-of-concept clinical trial to explore lifestyle or pharmacological interventions that have an effect on these blood factors. HeBe marks a significant step in translating scientific discoveries into potential interventions for age-related brain diseases, such as Alzheimer’s disease.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

The initial phase of HeBe focused on identifying individuals with extreme biological age phenotypes, determined through BrainAge computation from magnetic resonance imaging (MRI) data. This phase successfully delineated aging groups, including both "aged" and "rejuvenated" participants, setting the stage for the subsequent exploration of distinct blood factors associated with extreme age phenotypes.
The following step comprised comprehensive proteomic analyses on plasma samples from individuals exhibiting extreme biological age, categorizing them based on brain age relative to chronological age. Crucially, these analyses were sex-specific. Completion of these analyses on 340 samples marks a pivotal milestone for HeBe, providing a rich dataset currently under thorough analyses.
Furthermore, we conducted measurements of key Alzheimer's disease-related blood biomarkers in the ALFA cohort (https://www.barcelonabeta.org/en/alfa-study/about-the-alfa-study) identifying those blood biomarkers that indicate early amyloid- accumulation in the Alzheimer's continuum.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

The most notable results we have achieved thus far involve the identification of blood biomarkers that change in the early stages of Alzheimer's disease, a significant contribution to the evolving landscape of preclinical Alzheimer's blood biomarkers. These biomarkers will play a crucial role in evaluating the potential associations between the rejuvenating and aging blood factors we pinpoint and Alzheimer's disease along with neurodegeneration. Currently, we are in the process of analysing the proteomic data to discern the proteins linked to brain aging.
As we approach the conclusion of the HeBe project, our anticipated outcomes involve assessing whether these newly identified blood factors exhibit associations with cognition, neurodegeneration, and Alzheimer's disease biomarkers. The HeBe project will ultimately determine whether these blood factors may be therapeutic targets for age-related diseases such as Alzheimer’s disease.